Tau accumulation in the brain is a pathological hallmark of Alzheimer’s disease (AD) and other tauopathies. Quantitative visualization of tau pathology in humans can be a powerful method as a diagnostic aid and for monitoring potential therapeutic interventions. We established methods of PET quantification of tau pathology with 11C-PBB3 considering its radiometabolite entering the brain. Methods: Seven AD and seven healthy subjects underwent dynamic 11C-PBB3 PET scanning. Arterial blood was sampled to obtain the parent and metabolite input functions. Quantification of 11C-PBB3 binding was performed using dual-input models that take the brain metabolite activity into consideration, traditional single-input models without such considerations, and the reference tissue model (MRTMO) and standardized uptake value ratio(SUVR). The cerebellar cortex was used as the reference tissue for all methods.Results: The dual-input graphical models estimated binding parameter (BPND∗ ) stably (~0.36 in high binding regions). The MRTMO BPND∗ matched the corresponding BPND∗ by the dual-input graphical model (r2 = 1.00). SUVR-1 correlated very well with MRTMO BPND∗ (r2 > 0.97). However, BPND by the single-input models did not correlate with BPND∗ by the dual-input graphical model (r2 = 0.04). Conclusions: The dual-input graphical model BPND∗ is consistent with the reference tissue BPND∗ and SUVR-1, suggesting that these parameters can accurately quantify binding of 11C-PBB3 despite the entry of its radiometabolites into the brain.KEY WORDS: PET quantification, tau, 11C-PBB3, Alzheimer’s disease